The hormone GnRH may have potential for improving language, memory and other intellectual functions in people with Down syndrome, according to a pilot study
One in 800 children are born with Down syndrome, the most common genetic cause of intellectual disability. The vast majority of cases are caused by having three copies of chromosome 21 instead of two. People with Down syndrome also have reduced fertility, and their sense of smell is often impaired or lost. No treatments have been found so far for the neurological symptoms.
For people with Down syndrome, puberty brings a worsening of cognitive symptoms, and many experience a deterioration in smell. In a previous study, Prevot and his colleagues discovered that, just before puberty, a molecular “switch” is thrown that elevates GnRH levels. The switch involves molecules called microRNAs that are found in GnRH neurons, where they control GnRH release, which in turn regulates puberty.
The team studied mice that had three copies of their equivalent of chromosome 21 and displayed symptoms of Down syndrome. After seeing declines in olfactory and cognitive function and GnRH levels at puberty, the researchers set out to see if any of the changes were reversible. They had also observed that the functioning of the network of microRNAs and genes that controls the GnRH switch was out of balance, so they first tried increasing levels of one of the microRNAs.
The team then conducted a pilot study in seven adult men with Down syndrome. The treatment involved administering regular pulses of GnRH for six months using a mini pump that was inserted under the skin. Participants underwent cognitive tests and brain imaging to assess the status of brain connections before and after treatment. “Six out of seven patients improved their cognitive tests by 20 to 30 percent,” Prevot says.
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